Meta-analysis shows 6-months adjuvant trastuzumab is optimal

Adjuvant trastuzumab is just as safe and effective when given to HER2-positive early breast cancer patients for 6, rather than 12 months, according to a meta-analysis of >11,000 participants from 5 major clinical trials. This meta-analysis demonstrated that shorter durations of adjuvant therapy might be as effective.

Prof. Helena Earl (Addenbrooke's Hospital, UK) combined data on more than 11,000 patients who were treated with trastuzumab after surgery for their early HER2-positive breast cancer for 9 weeks or 6 months versus the current standard of 12 months [1]. The rationale for this analysis stemmed from the Finland Herceptin (FinHer) trial, which compared a shorter 9-week treatment protocol against no trastuzumab with promising results [2], and raised the question of whether shorter durations of adjuvant treatment may be just as effective. Additional benefits for patients could be lower toxicity, fewer hospital visits, and a more rapid return to normal life, with considerable societal benefits of reduced costs.

The meta-analysis included patient data from the PERSEPHONE [3], PHARE [4] and HORG [5] trials, which compared 12 months with 6 months (total n≈11,500), in addition to the SOLD [6] and Short-HER [7] trials, which compared 12 months with 9 weeks (total n≈3,500) adjuvant therapy, respectively. The primary endpoint of the meta-analysis was invasive disease-free survival (IDFS). Secondary outcomes were distant relapse-free survival, overall survival, and breast cancer-specific survival.

The investigators found that treating HER2-positive early breast cancer patients with adjuvant trastuzumab for 6 months was non-inferior to continuing treatment for 12 months, with no significant difference in 5-year IDFS rates (89.26% vs 88.56%, respectively; HR 1.07; 90% CI 0.98–1.17; P=0.02). Importantly, however, when 9 weeks of trastuzumab was compared with 12 months, the IDFS rates were lower for the shorter duration of treatment, not reaching the pre-specified non-inferiority limit, indicating that 9 weeks was not as beneficial as 12 months of treatment (91.40% vs 89.22%, respectively; HR 1.27; 90% CI 1.07–1.49; P=0.56). Combining all 5 trials to compare 12 months of adjuvant therapy versus <12 months showed 5-year IDFS rates of 88.46% versus 86.87%, respectively (HR 1.14; 95% CI 0.88–1.47; P=0.37).

The authors concluded that although efficacy outcomes at 6 months were non-inferior to those at 12 months of adjuvant trastuzumab, 9 weeks of adjuvant treatment was indeed inferior.

1. Earl HM, et al. Individual patient data meta-analysis of 5 non-inferiority RCTs of reduced duration single agent adjuvant trastuzumab in the treatment of HER2 positive early breast cancer. Abstract LBA11, ESMO Congress 2021, 16–21 September.
2. Joensuu H, et al. N Engl J Med. 2006;354(8):809-20.
3. Earl HM, et al. Lancet. 2019;393(10191):2599-2612.
4. Pivot X, et al. Lancet. 2019;393(10191):2591-2598.
5. Mavroudis D, et al. Ann Oncol. 2015;26(7):1333-40.
6. Joensuu H, et al. JAMA Oncol. 2018;4(9):1199-1206.
7. Conte P, et al. Ann Oncol. 2018;29(12):2328-2333.

 

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Posted on 19 November, 202129 February, 2024